Defects on human facial skeleton caused by blast injury or deformity due to ablation of tumor lead to devastating physical and mental trauma for a patient. Such incidents commonly result in a bone loss in the facial skeleton which destroys structural integrity. Reconstructive surgery is necessary to revive adequate load-transfer mechanism in the facial skeleton, to support the orbital content and to restore functional and aesthetic role. Bone taken from the same patient is often cut and reshaped by osteotomy surgery then placed into the region of bone loss. The surgical outcome therefore not only depends on the size of the defect but also on expertise of the surgeons. Computer aided design with topology optimization which can restore the functions of bone replacements can be a viable alternative. In this research, a state-of-art three dimensional (3D) multi-resolution topology optimization is used to design patient-specific bone replacement shapes for patients with different defects. Bone replacements are inserted into the region of defect using computer-aided design software. Prototypes are fabricated with a 3D printer to explore the mechanical characteristics and behaviors under realistic human mastication loadings. Finite element analysis is also conducted with experimentally obtained printing material properties. Results indicate that topology optimized solutions not only can revive adequate load-transfer mechanism in the facial skeleton but also withstands maximum mastication force found in the literature.